Process design and management system

ABSTRACT

A process design and management system for batch manufacturing of pharmaceuticals products. The system permits a user to create a chemical process design based on the user&#39;s input data and retrieved process library data which includes material data, process data, and equipment data. The system includes software objects defining operations sequences, and processing operation parameters including materials flows and balances, cycle time, constraints, equipment, generic equipment capability requirements, specific equipment capability requirements, and actual capacity analysis. A graphical user interface allowing multiple views of the chemical process design, including one or more of a design view, process flow view, time cycle view, and instructions view.

FIELD OF THE INVENTION

The present application relates to systems for process design andmanagement in the manufacturing of chemical products, particularlychemical and biologic pharmaceutical products, as well as food productsand cosmetic products, with particular application for batchmanufacturing processes of such products.

BACKGROUND OF THE INVENTION

The process of bringing a pharmaceutical to market can take years, andrequire a substantial capital investment. The required research andclinical trials are lengthy and time-consuming, but the regulatoryapproval is only the start of what is a complex process to produce anddeliver product on a commercial scale. Once the U.S. Food and DrugAdministration (“FDA”) approves a drug, pharmaceutical engineers,chemists, and plant managers then prepare the pharmaceutical for massproduction.

In pharmaceutical production, the key product to be produced is what isknown as the active pharmaceutical ingredient (“API”). Typically, duringpremarketing development and clinical trials the API has only beenproduced in very small quantities on a lab bench scale. In a typicalpharmaceutical production timeline in the United States a new productapplication (NDA) is submitted to the FDA (or equivalent regulatoryauthority in other countries or regions) together with a productionprocess with basic parameters usually developed in the research lab. Theprocess is then further developed for improvement in terms of yield,purity, economics, raw product availability; etc. Subsequently the benchscale “recipe” for the API, which often exists only on paper, must bescaled up to a manufacturing plant scale recipe to accommodatecommercial production. The process design for commercial production of anew API can take many months. Once the manufacturing plant scale recipeis developed, the manufacturing process design is developed and tested.Operating instructions are prepared and a recipe is formulated for aproduction execution system which may comprise a DCS (distributedcontrol system), or an Electronic Work Instruction, or other processor,or any combination of these computer based execution systems. A solventor water run or dry run (if required), or other offline productionsimulation run is then effected to fine tune the system before theproduction campaign (which defines a sequence of one or more batches) isrun. Batches of product (active pharmaceutical product or API) arereleased, with notation of deviations, changes and review. A constantmonitoring and analysis of all the manufacturing information ismaintained. Deviations from the predicted process design and fromquality standards are recorded and investigated both for internalreasons and FDA compliance reasons. Problems with the process design areoften uncovered when commercial production challenges emerge over time,and the process may need to be revised and/or the recipe may need to bereformulated until a consistent API product is delivered. All thesesteps can consume substantial time and expense and must be documented.

Process control systems that produce batches of products typicallyinclude a graphical interface, which enables a user (e.g., an engineer)to define and store one or more basic product recipes, batch parameters,equipment lists, etc. These basic product recipes typically include asequence of process steps that are each associated with or bound to aparticular equipment list. In binding recipe process steps to particularpieces of equipment, the user (e.g., an operator) explicitly defines,prior to the batch execution of the recipe, which piece of processcontrol equipment to be used to carry out each process step of therecipe. Additionally, each of the process steps may require a user(e.g., an operator) to define one or more input/output (I/O) batchparameter values that are used during the execution of a batch tocontrol the sequence and/or timing of equipment operations, set alarmlimits, set target control values (e.g., set-points), etc. These I/Oparameter values may be associated with inputs and outputs that are sentto or which are received from one or more of the field devices withinthe process control system or, alternatively, may be intermediate orcalculated values that are generated by the process control systemduring the execution of a batch. Thus, in defining a batch, a user(e.g., an operator) typically uses the graphical interface to select abasic product recipe (which includes specifications that bind theprocess steps of the recipe to process control equipment) and to specifythe parameter values that are to be used during execution of the batch.

Once a batch product recipe is perfected, it is exclusive to one plant.Historical differences in product lines at different facilities,combined with years of corporate mergers, spinoffs, and reorganizations,mean that even a single company has manufacturing plants each with aunique collection of equipment and systems, such that a recipe thatworks in one plant cannot easily be transferred to another plant, due toequipment differences, without substantial re-engineering of the recipe.Although systems have been proposed to automate the commercial scalerecipe and process design, they have not delivered a fully enabled,operative system, and thus many of the above steps are typicallymanually determined and are not automated.

Additionally, manufacturing efficiency programs lead to ever morecomplex problems of process control and synchronization. Many modernbatch process plants run several parallel batches using multiple sets ofequipment, or sets of operatively connected control equipment units.Recipes have become more complex, increasing the number of proceduralsteps. Better real-time measurements of process parameters detectabnormal conditions such as, excess temperature, insufficient pressure,or an unexpectedly high concentration of a particular chemical. Systemsdesirably respond to these conditions as quickly as possible in order toreduce product loss and to avoid harmful situations.

In addition, government regulation of pharmaceutical batch manufacturingcontinues to become more exacting. The Food and Drug Administration ofthe United States (FDA) in 2003 launched the so-called Process AnalyticTechnology (PAT) initiative. The stated goal of PAT is to control themanufacturing process in addition to final manufactured products. Tocomply with PAT requirements, manufacturers must be able to assurequality at the intermediate steps of a corresponding manufacturingprocess and properly and timely respond to detected out-of-specificationconditions.

Accordingly, there is a need for a fully integrated process design andmanagement system for process manufacturing which is robustly adapted tooperate at both a generic master recipe level and at a specific facilityand equipment level.

SUMMARY OF THE INVENTION

A process design and management system comprising: a General Designdigital software object allowing a user to assemble a process designbased on the user's input data and retrieved process library data, theGeneral Design software object defining operations sequences, andprocessing operation parameters including materials balances, cycletime, and constraints; the process library data being digital data, theprocess library data including material data, process data, andequipment data; a General Master Design digital software object allowinga user to derive a generic equipment process, the General Master Designsoftware object defining operations equipment sequences, and processingoperation parameters including equipment, generic equipment capabilityrequirements, materials balances, cycle time, and constraints; and aMaster Design digital software object allowing a user to derive aplant-specific equipment process, the Master Design software objectdefining operations equipment sequences, and processing operationparameters including specific equipment, specific equipment capabilityrequirements, actual capacity analysis, materials flows and balances,cycle time, and constraints. Preferably, the system further includes ashop floor execution system processing object for creating a MasterRecipe associated with the plant-specific equipment process. The systemaccording to the present teachings provides a library of design objectsthat can be used to easily design a manufacturing plan through the userinterface.

The graphical user interface allows multiple views of the processdesign, generic equipment process, and plant-specific equipment process.The graphical user interface views include one or more of a design view,process flow view, time cycle view, and instructions view. The designview identifies each equipment unit and lists the sequential processoperations within each equipment unit; the process flow view displaysinter-equipment connections and material transfers for the process; andthe time cycle view displays start time, end time, slack time andduration for each operation of the process in order. The instructionsview displays detailed manufacturing work instructions which include thekey targets, ranges and textual description of the process. The designview, process flow view, instruction view and time cycle viewdynamically interact with each other such that a change in one view willresult in a corresponding change in the others.

One embodiment of a method for using the system to design a processincludes the steps, but is not limited to: preparing a General Designusing the user interface by selecting operations and constraints for theprocess, the operations and constraints defined in a system library;deriving a General Master Design from the General Design using the userinterface, including adding equipment requirements and defining genericphases; deriving a Master Design from the General Master Design usingthe user interface, including defining specific equipment for a plantand mapping the generic phases to specific phases for the plant; andgenerating a Master Recipe from the Master Design for display throughthe user interface as instructions.

In one embodiment, the system allows users to simulate a design in orderto validate the design model. This includes providing any validationerrors encountered during the simulation to the user through the userinterface.

In one embodiment, the system tracks each process step execution,equipment use, and material use, and lets the user manually orautomatically adjust the process design for future batches. The batchmanufacturing process and/or process recipe may have associated globallyunique identifiers for each process ingredient and process step thatpermit the tracking of ingredients and the process steps of the processto enable a persisted correlated execution history. This way, multiplebatch manufacturing process and/or process recipes may be correlated todetermine process deviations in process equipment. Archived process datacan be correlated across the product lifecycle, even where a MasterDesign has changed.

Other embodiments of the system and method are described in detail belowand are also part of the present teachings.

For a better understanding of the present embodiments, together withother and further aspects thereof, reference is made to the accompanyingdrawings and detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a diagram of one embodiment of a process design andmanagement system in accordance with the present application.

FIG. 1B is a diagram of the relations between software objects and dataobjects in one embodiment of a process design and management system inaccordance with the present application.

FIG. 2 is a diagram of a process hierarchical task assembly in a processdesign and management system in accordance with the present application.

FIG. 3 is a UML class diagram showing the object oriented architectureof operations and generic phases in a process design and managementsystem in accordance with the present application.

FIG. 4 is a UML class diagram showing the object oriented architectureof constraint processing in a process design and management system inaccordance with the present application.

FIG. 5 is a diagram of equipment requirement processing task assembly ina process design and management system in accordance with the presentapplication.

FIG. 6 is an illustration of a process flow layout in a process designand management system in accordance with the present application.

FIG. 7 is a UML class diagram showing the object oriented architectureof equipment requirement processing in a process design and managementsystem in accordance with the present application.

FIG. 8 is a UML class diagram showing the object oriented architectureof specific equipment selection processing in a process design andmanagement system in accordance with the present application.

FIG. 9 is a diagram of an example shop floor execution system map in aprocess design and management system in accordance with the presentapplication.

FIG. 10 is a UML class diagram showing the object oriented architectureof execution system phase mapping in a process design and managementsystem in accordance with the present application.

FIG. 11 is a UML class diagram showing the object oriented architectureof execution history correlation processing in a process design andmanagement system in accordance with the present application.

FIG. 12 is an illustration of a layout for a graphical user interface ofa process design and management system in accordance with the presentapplication.

FIG. 13A is an example of a graphical user interface of a process designand management system in accordance with the present application,showing a process design layout, “Design” which includes units andoperations, “Process Flow” which includes equipment and connections,“Time Cycle” (a Gantt chart of the manufacturing time cycle), and“Limits View” (constraints).

FIG. 13B is an example of a “PV Trend” (a process variable chart) in agraphical display window in the graphical user interface of FIG. 13A.

FIG. 13C is an example of “Instructions” (a Master Recipe instructionset) in a window in the graphical user interface of FIG. 13A.

FIG. 13D is an example of “Mixture” (a reagent mass balance chart) in awindow in the graphical user interface of FIG. 13A.

FIG. 14 is an example of a graphical user interface of a process designand management system in accordance with the present application,showing a process design layout, “Design” which includes units andoperations, “Time Cycle” (a Gantt chart of the manufacturing timecycle), and “Instructions” (Master Recipe instruction set).

FIG. 15 is an example of a graphical user interface of a process designand management system in accordance with the present application,showing a process design layout, “Design” which includes units andoperations, “Process Flow” which includes equipment and connections, and“PV Trend” (process variable chart).

FIG. 16 is an example of a graphical user interface of a process designand management system in accordance with the present application,showing a process design layout, “Design” which includes units andoperations, “Process Flow” which includes equipment and connections, and“Instructions” (Master Recipe instruction set).

FIG. 17 is an example of a graphical user interface of a process designand management system in accordance with the present application,showing a “Product Browser” view, which includes a high level chart ofprocess steps, a Gantt chart of the manufacturing time cycle, andMetrics analyzing product manufacturing cost for different batch sizesof product.

DETAILED DESCRIPTION OF THE INVENTION

The present teachings are described more fully hereinafter withreference to the accompanying drawings, in which the present embodimentsare shown. The following description is presented for illustrativepurposes only and the present teachings should not be limited to theseembodiments. Any computer configuration and architecture satisfying thespeed and interface requirements herein described may be suitable forimplementing the system and method of the present embodiments.

We refer to and incorporate by reference our U.S. Pat. Pub. No.2007/0050070 as well as U.S. Provisional Patent Application Ser. No.62/063,625 filed 14 Oct. 2014 in their entireties.

Referring to FIG. 1A, a process design and management system 100 isshown; and FIG. 1B shows the relationship between the software objectsof Design System 102 in process design and management system 100 anddata objects created in Design System 102. Design System 102 whichbegins with a “General Design” object 110 that defines the processdesign, also referred to as the General Design 111. The General Designprocess definition is transformed to a generic equipment class basedprocess sequence, which is referred to herein as the “General MasterDesign” 113 by General Master Design object 112. The General MasterDesign is used to create a “Master Design” 115 which is specific to aparticular manufacturing plant and its equipment with equipment specificphases by Master Design object 114. Finally, a “Master Recipe” 117 whichcontains the manufacturing instructions which list all required inputsand steps, is created by the Master Recipe Object 116 of Design System102 and used in automated and/or manual manufacturing execution systemssuch as DCS (Distributed Control System) 120. DCS 120 controls andmonitors the process and manufacturing steps executed by Equipment 122,124, through 124 _(n). Instrumentation and measuring apparatus providedin Equipment 122, 124, 124 _(n) provide process parameter measurementdata 126 which is monitored by DCS 120 and continuously or periodicallyrecorded in Process Data Archive 130. The process parameter measurementdata 126 may optionally also be monitored by the system 100 in real timeor through review of the Process Data Archive 130. Because the systemmay interact with plant manufacturing systems, it may receive real-timeinformation concerning the status of plant equipment. This allows thesystem to both monitor multiple plants on a global scale, as well as todistribute the efficient manufacture of drugs to multiple plants,providing for true science based quality by design project planning on aglobal scale.

Process Library 102 supports the General Design object 110 with alibrary of predefined unit operations that can be used to populateGeneral Design object 110. Generic Equipment Library 104 supports theGeneral Master Design object 112 with a library of predefined equipmentclasses that can be used to operate the processes of General Designobject 110. Specific Equipment Library 106 supports the Master Designobject 114 with a list of available equipment at particular plantlocations.

The General Design object 110 is intended to define the processsequence, material inputs and outputs and transfers, reactions andtransformations, and constraints. This level of design may not beassigned to equipment or have detailed equipment-level activitiesdefined. Preferably, it has equipment-independent process definitions.The General Design may be seen as the container for the level ofinformation that would ordinarily be contained in a regulatory filing.It is not intended to be a design that would contain all the informationnecessary for transfer to manufacturing, but rather a container of thefoundational process knowledge associated with chemical, physical, orbiological transformations and the appropriate quality controlconstraints.

The General Design object 110 may incorporate concepts defined in S88for ‘General Recipes’. The most widely adapted standards formanufacturing control systems in the US and Europe are ISA S88.01 andIEC 61512-01 respectively (the disclosures of which are incorporated byreference). These standards refer to various models such as equipmentmodels and recipe models and the various objects and components involvedin manufacturing and batch control. Terminology and methodology usedhereinafter are with respect to those defined in such standards andparticularly in ISA S88.01 (S88).

General Design object 110 defines the essential process sequence, withassociated process parameters, and with constraints (e.g., limits) whereappropriate. In pharmaceutical manufacturing, constraints defined in theGeneral Design object 110 may be regulatory constraints pertaining toproduct safety. Regulatory limits may be defined, classified andassigned to operations. For example, regulatory parameters andin-process controls may be defined and classified as critical qualityattributes (“CQA”) that impact the safety or efficacy of a product,critical process parameters (“CPP”) that influence a CQA and that mustbe controlled within predefined limits to ensure the product meets itspre-defined limits, key process parameters (“KPP”) that influenceproduct quality or process effectiveness, and key quality attributes(“KQA”) that have a potential to impact product quality or processeffectiveness, among others. Other types of information may be compiledat this stage. For example, process definitions (e.g., operations) allowfor a calculation of time cycle, instruction text, and material usagesummary, among others.

Process Library 102 may be used to build the General Design 111. A usercan also apply an “envelope” around several contiguous operations thatmay flow across several process units. This envelope may be referred toas a stage or operation group and used to support analysis and historycorrelation.

Once completed, the General Design 111 may be approved and locked suchthat it can only be modified by creating a new revision. Full electronicapproval and audit trail may be maintained. Multiple General Designs 111may be active, to take account of different sequencing options ordiffering requirements in different markets, for example.

The General Master Design 113 is an extension of the General Design 111that enables the user to apply more equipment based information to adesign. While the General Master Design 113 may not be site/equipmentspecific, it can add significant equipment-level operating details.Operations may be broken down into lower-level actions or steps. Thelower level steps are referred to as Generic Phases. The General MasterDesign 113 may be populated with generic phases and generic equipmentclasses and capability selections from the Generic Equipment Library104. Equipment classes/characteristics may be defined, generic phasedetail added under each operation, and quality and action constraintsdefined. General Master Designs 113 can be used by any site and multipleversions may co-exist to address different equipment types (e.g.,Nutsche filter vs. centrifuge, etc.) or different equipment trainconfigurations.

Selecting equipment from a particular manufacturing plant transforms aGeneral Master Design 113 to a Master Design 115. The equipmentselection may involve a list of equipment with adequate capabilities forthe process. A Master Design 115 may incorporate concepts defined by S88for “Master Recipes.”

At this level, specific details may be added that make the designspecific to equipment in a specific manufacturing facility. MasterDesigns 115 are therefore site equipment dependent. The Master Design115 may be developed using specific equipment and capability selectionsSpecific Equipment Library 106. The Master Design object 114 allows theuser to assign actual equipment and to map the generic phases tospecific (local site) execution system objects like phases and equipmentcontrol modules. Site/equipment (or classes) may be selected, equipmentoperating details added, and process control constraints defined. MasterRecipe 117 details and batch instructions may also be defined in theMaster Design object 114 and/or Master Recipe object 116. Master Recipe117 desirably is specifically written to integrate with a plant'sexisting manufacturing systems such as a distributed control system(“DCS”), laboratory information management system (“LIMS”), ormanufacturing execution system (“MES”), providing a recipe specificallytailored for the plant.

The Master Recipe 117 is typically duplicated and used as the controlrecipe for each batch that is manufactured. Each control recipe willhave additional data assigned or obtained during manufacturing, forexample, batch ID, specific material lots consumed and produced, andwhich specific equipment was used for the batch.

General Design object 110 begins with a series of steps which constitutea General Design 111, which is a design hierarchical task assembly asillustrated in FIG. 2. The process design has one or more units(fundamental process equipment or work center) such as Unit A 140 andUnit B 142. Each unit has a sequence of operations such as 144, 146,148, 150 and 152 that are created from operation definitions whichcollectively represent one simulated process stream. Operationdefinitions are reusable software objects selected from Process Library102 that characterize physical, chemical, or biological process steps inthe process stream. Operation definition software takes unit equipmentclasses, operation parameters, and synchronized operation parametersinto account to create a sequence of subordinate generic phases 160 thatare created from generic phase definitions. Generic phase definitionsare reusable software objects that characterize physical, chemical, orbiological process steps with associated generic equipment requirementsspecifically designed to be the building blocks in a General MasterDesign 113. Generic phases 160 inherit parameters and synchronizationsfrom their parent operation and represent the next level of detail inthe evolution of a process design.

Cycle time processing of generic phases 160 is controlled by theoperation definition. Each generic phase 160 definition has a specificduration formula based on the physical, chemical, or biologicaltransformation of the process step and the associated abstract equipmentperformance parameters. Duration formulas contain variables based onuser input, facility, and equipment classes. The duration of eachoperation and generic phase in a process design is calculated. Anoperation can include time-based synchronization with one or moreoperations in other units (for example, material transfer between OperA.3 148 & Oper B.2 152 shown in FIG. 2), and in the similar way, ageneric phase can simulate time-based synchronization with one or moregeneric phases in other Units (e.g. GPhse A.3.2 & GPhse B.2.2).

Materials balance processing is determined by the General Design object110. Material balances are determined based on the parent operation andthe generic phase. Optionally the system permits a user to add one ormore materials into the processing stream of a unit (e.g. Oper A.1 144)or transfer some or all of the mixture in a unit processing stream toanother unit processing stream via a synchronized Operation (e.g. FromOper A.3 148 to Oper B.2 152). A mass balance simulation engine detectspotential transformations and performs the appropriate changes to themixture in the unit process streams. A design mass balance graph isautomatically generated and maintained during process designconstruction using the generic phase processing stream and the transferconnections between them, including material additions, transfers, andtransformations.

A UML (Unified Modeling Language) Class Diagram showing the architectureof General Design object 110 of system 100 and the major objects thereinand their interaction in the development of a process design isillustrated in FIG. 3. In the FIGS, library data scope 170 objectscontain objects that constitute design construction methods and rulesand may be located in Process Library 102 and/or Generic EquipmentLibrary 104. Reference data scope 172 objects are objects that definespecific customer or plant location data and may be stored in SpecificEquipment Library 106. Design data scope 174 objects are objects thatstore design knowledge. History data scope 176 objects are objects thatstore process data history and may be located in Process Data Archive130.

Operations form the key building blocks that a user interacts with inGeneral Design object 110, and to add more operational data in GeneralMaster Design object 112. When used in the General Design object 110,high level information is entered by the user, for a given operation, todefine the process sequence. The user creates operation objects andconnections between operation port objects manually, but design system102 creates generic phase objects and connects generic phase portobjects automatically by executing dynamic code that performs genericphase insertion and parameter mapping.

When the engineer reviews the same operation at the General MasterDesign object 112 level, additional information is required to beentered. Equipment capability requirements and other low level equipmentactivities that need to be performed in a manufacturing location aredetermined to define what the operation requires from a processperspective. Once all the detailed operation parameters are entered atthe General Master Design object 112, design system 102 determines whatgeneric phases 160 are needed for that Operation to be executed using astandardized best practice approach. Generic phases 160 define lowerlevel equipment activities. System 100 maintains separate libraries ofdefinitions for operations and generic phases 160. In many cases thesame activity exists in both libraries with the generic phase levelhaving more granular processing steps with additional details thatimpact design performance and quality. Both are non-plant specific orgeneric entities.

Material entities may facilitate mass balance and energy balancesimulation and may include:

-   -   ● Class entities that have parameter definitions for specific        design relevant data such as atomic, physical, and thermal        properties    -   ● Definition entities that store specific materials and their        properties (mixtures are stored as definition hierarchies)    -   ● Specification entities that store variants of the same        material that differ in ways that do not affect simulation        results, but are critical to process understanding (e.g. grain        size variants, impurity variants, etc.)

Product, product step, and process path entities may facilitate theeffective management of the top level design information for globalprocess step paths. In many process industries the number of processingsteps is too large to practically manufacture in a single facility. Aproduct step process can be modeled as a directed acyclic graph ofprocess steps. Each process step can represent either reaction basedtransformations or material specification based transformations.

Equipment and resource class hierarchies may support design by providingparameter definitions for class specific properties. They may alsoprovide a library of industry specific classes organized in logicalhierarchies that include parameter definition inheritance from parentclasses to child classes. The equipment classes may also provide thefoundation for operation to generic phase mapping that can be driven byone or more equipment classes.

To facilitate equipment requirement simulation, dynamic equipmentselection, and equipment switching during the design process, equipmentdetail may be modeled using capability and physical component entities.Both capability and physical component class hierarchies may supportdesign by providing parameter definitions for class specific properties.They also may provide a library of industry specific classes that areorganized in logical hierarchies that include parameter definitioninheritance from parent classes to child classes. The capability classhierarchy may also have a function which provides the foundation forequipment requirement specialization where the higher level is lessspecialized and the lower level is more specialized (e.g. variable speedmixing vs. 2-speed mixing, liquid-inlet vs. water-inlet, etc.).

A facility may be used to store site specific knowledge such as localdesign preferences, language selection, and local costing data. The toplevel facility may be the global facility where all library data, globalreference data (such as materials) and General Designs are stored. Thesecond level in the hierarchy may represent site facilities thatrepresent physical locations (such as a research or manufacturingcampus) and may be used to store shared reference data (such as utilityresources and mobile equipment). A third level in the hierarchy mayrepresent lab or manufacturing locations (buildings or rooms) and may beused to store local reference data (such as equipment) and GeneralMaster and Master Designs. Users may have roles in multiple facilities,but their default preferences may be loaded from their home facility.

To accommodate facility specific equipment and process requirements,capability and resource specialization rules may be defined in eachfacility. The design application may use these rules to convert genericcapability or resource requests into more specific capability orresource requests (e.g. liquid-inlet into water-inlet, receiver-tankinto solvent-receiver-tank). Rule processing may be performed in thefollowing sequence:

-   -   ● Specialization is performed via the material consideration        entities where the material transfer records are searched    -   ● Injection is performed via the capability class resource class        entities where a search is performed for the capability requests        that require specific resource request    -   ● Consolidation rules are performed to compute equipment        capability requirements and resource requirements The user can        also specialize the capability requests and resource request        manually.

Material transfers may be consolidated and mapped to unit inlets,outlets, and logical inter-unit connection requirements. Generic phasesmay generate one or more equipment capability requests. Equipmentcapability requests may be consolidated into equipment capabilityrequirements based on shareable capability rules and facility specificrules. Generic phases may generate one or more resource requests.

One skilled in the art would appreciate the different entities that maybe used in accordance with the present teachings, which are not limitedto any particular embodiment disclosed herein. In addition, entities maycontain dynamic code which is defined as code that is injected into theapplication at runtime. The dynamic code capability may be used to allowfor application extensibility without the need to change and revalidatethe core system foundation, which is desirable in keeping the cost ofchange management low in a regulatory environment

Referring again to the software architecture illustrated in FIG. 3, theLibrary Data Scope 170 contains Unit Definition (“UnitDefinition”),Operation Definition (“OperationDefinition”), Operations Port Definition(“OperationPortDefinition”), Generic Phase Definition(“GenericPhaseDefinitions”) and Generic Phase Port Definition(“GenericPhasePortDefinition”) objects. A Generic Phase Creator(“GenericPhaseCreator”) functionality is available. The Design DataScope 1130 contains a General Master Unit (“GMUnit”) which is in turncomposed of the General Master Operation (“GMOperation”) and GeneralMaster Capability Requirement (“GMCapabilityRequirement”) objects. Thecomposition of the General Master Operation includes the General MasterOperation Port (“GMOperation Port”) and General Master Generic Phase(“GMGenericPhase”) objects. The composition of the General MasterGeneric Phase includes the General Master Capability Request(“GMCapabilityRequest”) and General Master Generic Phase Port(GMGenericPhasePort”) objects. The General Master Operation isassociated with the Operation Definition object, the General MasterOperation Port is associated with the Operation Port Definition, theGeneral Master Generic Phase is associated with the Generic PhaseDefinition, and the General Master Generic Phase Port is associated withthe Generic Phase Port Definition.

The system 100 objects provide a framework for hierarchical taskassembly, with the ability to (1) capture the science/chemistry of theprocess; (2) transform the process definition to a generic, equipmentclass based process sequence; (3) switch equipment classes in theprocess if desired; and (4) transfer the process from one manufacturingplant to another and generate a customized recipe appropriate for thetarget plant.

A significant consideration in the General Design object 110 isconstraint processing. Constraints are regulatory or qualitylimitations, for example, “reactant y must never exceed 120° C.” or “theconcentration of solute z must be below 6,200 ppm in solution.” Inaddition to process design level constraints such as the above, theremay be equipment constraints, for example, in the Master Design 115level, the plant facilities may have mixing vessel of limited size, andthe proposed General Design 111 might be unworkable if the batch sizewould exceed the vessel capability. Constraint definitions are reusablesoftware objects that define constraints and are used in validation of asimulated process stream. A user can select one or more constraints froma library of constraint definitions to add a unique constraint instanceto the General Design 111. Each constraint instance must be mapped toone or more operations or generic phases based on the mapping rulesimposed by the constraint definition. Constraints inherited from aGeneral Design 111 cannot be removed by the user in lower level GeneralMaster 113 or Master Designs 115. During simulation cycles, constraintviolations are reported to the user. Also, a user can optionally map aconstraint to one or more operation parameters to define cause-effectrelationships.

A UML Class Diagram showing the architecture of constraint processing inGeneral Design object 110 of system 100 is illustrated in FIG. 4. Theconstraint framework is used to store design knowledge that definecritical boundaries that are tracked to manage product quality.Constraints that are created in the General Design object 110 representregulatory requirements or critical boundaries. They are copied to theGeneral Master Design object 112 as locked objects. A user willtypically create additional constraints at the General Master Design 113level to add additional knowledge related to product quality,environmental, legal, or other reasons, and manually associate them withone or more operations and generic phases. Users can optionally addoperation dynamic parameter associations to document important cause andeffect relationships between an upstream operation and a downstreamoperation where quality sampling is required.

Referring to the constraint processing software architecture illustratedin FIG. 4, the Library Data Scope 170 contains Constraint DefinitionParameter Definitions (“ConstraintDefinitionParameterDefinition”) andConstraint Definitions (“ConstraintDefinition”). The Design Data Scope174 shows the General Constraint (“GConstraint”) as an object which ispart of the General Design object 110 (“GDesign”) and the General MasterConstraint (“GMConstraint”) which is part of the General Master Designobject 112 (“GMDesign”). FIG. 4 illustrates the previously describedGeneral Unit (“GUnit”) as an object in the General Design object 110,the General Operation (“GOperation”) as an object in the General Unit,and the General Operation Dynamic Parameter (“GOperationDynamicParameter”) as an object in the General Operation. The composition ofthe General Constraint includes General Constraint General Operation Map(“GConstraintGOperationMap”); General Constraint General OperationDynamic Parameter Map (“GConstraintGOperationDynamic ParameterMap”); andGeneral Constraint Dynamic Parameter (“GConstraint Dynamic Parameter”)objects. The General Constraint General Operation Dynamic Parameter Mapis associated with the General Operation Dynamic Parameter; and theGeneral Constraint General Operation Map is associated with the GeneralOperation object. The General Constraint Dynamic Parameter is associatedwith the Constraint Definition Parameter Definition in Library DataScope 170. FIG. 4 also illustrates the previously described GeneralMaster Unit (“GMUnit”) as an object in the General Master Design object112, the General Master Operation (“GMOperation”) as an object in theGeneral Master Unit, and the General Master Operation Dynamic Parameter(“GOperationDynamic Parameter”), the General Master Generic Phase(“GMGenericPhase”) as objects in the General Master Operation. Thecomposition of the General Master Constraint includes General MasterConstraint General Master Operation Map (“GMConstraintGMOperationMap”);General Master Constraint General Master Operation Dynamic Parameter Map(“GMConstraintGMOperationDynamic ParameterMap”); General MasterConstraint General Master Generic Phase Map(“GMConstraintGMGenericPhaseMap”) and General Master Constraint DynamicParameter (“GMConstraint Dynamic Parameter”) objects. The General MasterConstraint General Master Operation Dynamic Parameter Map is associatedwith the General Master Operation Dynamic Parameter; the General MasterConstraint General Master Operation Map is associated with the GeneralMaster Operation; and the General Master Constraint General MasterGeneric Phase Map is associated with the General Master Generic Phaseobject. The General Master Constraint Dynamic Parameter is associatedwith the Constraint Definition Parameter Definition in Library DataScope 170.

The constraint processing objects provide the system 100 with ability toautomatically validate changes in the General Design against any and allconstraints known to the System. Further, when system 100 is run in asimulation mode, it allows the user to identify and evaluate both directand indirect cause and effect outcomes arising from process changes inthe General Design.

FIG. 5 illustrates the extension of a General Design 111 to a GeneralMaster Design 113. Equipment requirement processing determines requiredattributes of equipment needed to implement the General Design 111.Material (M) flows and transfers mapped to unit inlets (i1, i2) and unitoutlets (o2), and inter-unit connection requirements are determined. Thepreviously defined generic phases can generate one or more equipmentcapability requests (c^(A), c^(B)) and associated resource requests (R¹,R²) which define direct and indirect instrumentation, consumable, sharedutility or labor needs. In this step the sequential or parallel natureof the different process actions are considered and where possibleprocess requests are consolidated and/or equipment capability andresource requests are consolidated to minimize the total requiredequipment and resources. The equipment capability requests are finalizedas General Master Design 113 equipment capability requirements. Aprocess flow layout as shown in FIG. 6 is diagrammed based on theGeneral Master Design 113. FIG. 6 shows a series of reactor vessels 190,192, 194, 196 and other equipment and the component flow paths as arrowsin the layout.

A UML Class Diagram showing the architecture of equipment requirementprocessing in General Master Design object 112 in system 100 isillustrated in FIG. 7. In FIG. 7, the Library Data Scope 170 contains“ResourceClass”, CapabilityClass” and “MaterialClass” objects. Theseobjects in turn receive data from “CapabilityClassResourceClassMap”,“MaterialConsideration”, “Material Definition”, and “MaterialDefinitionMaterialClassMap” objects in Reference Data Scope 172. A“MaterialSpecification” object in Reference Data Scope 172 informs the“MaterialDefinition” object. The Design Data Scope 174 shows the GeneralMaster Generic Phase (“GMGenericPhase”) which determines generic phasesusing equipment data from the Library Data Scope 170 and Reference DataScope 172. In particular, General Master Generic Phase includes GeneralMaster Phase Port (“GMPhasePort”), and General Master Capability Request(“GMCapabilityRequest”) objects; and has an associated General MasterMaterial Transfer (“GMMaterialTransfer”). The General Master CapabilityRequest includes a General Master Resources Request(“GMResourceRequest”) object. These objects interact with the“ResourceClass”, “CapabilityClass” and “MaterialClass” objects todetermine a General Master Design 113. Capability and resourcespecialization rules can be defined in each object. In such cases,system 100 uses these rules to convert generic capability or resourcerequests into more specific capability or resource requests (e.g.liquid-inlet into water-inlet, receiver-tank intosolvent-receiver-tank).

The equipment requirement processing objects provide the system 100 withdynamic equipment selection and mapping, allowing the General Design 111to be applied to any manufacturing plant or multiple manufacturingplants. Further, it provides an automatic definition of equipment trainsetup and connections.

The General Master Design 113 is implemented as a Master Design 115through specific equipment selection processing. Equipment selectionprocessing steps begin by identification of all equipment that could beused by a unit in a General Master Design 113. The units areprovisionally selected for use in the General Master Design 113, and theactual capacity of the identified equipment is analyzed to determine ifthe equipment is capable of satisfying the General Master Design 113.The actual capacity algorithm includes analysis of pipe, inlet andvessel capabilities (e.g. for example, whether different materialcharging capabilities share the same physical inlet component).Equipment having the required capabilities is identified and a MasterDesign 115 is developed.

A UML Class Diagram showing the architecture of specific equipmentselection processing in Master Design object 115 in system 100 isillustrated in FIG. 8. As seen therein, Design Data Scope 174 usesphysical component data from the Library Data Scope 170 and ReferenceData Scope 172. Library Data Scope 170 includes “CapabilityClass” and“PhysicalComponentClass” objects. Reference Data Scope 172 includes the“Equipment” object which includes “Capability,” “PhysicalComponent”, and“CapabilityPhysicalComponentMap” objects. The Design Data Scope 174shows the previously described General Master Unit (“GMUnit”), GeneralMaster Operation (“GMOperation”), and General Master Generic Phase(“GMGenericPhase”) objects and additionally shows the General MasterCapability Requirement (“GMCapabilityRequirement”) along with thepreviously described General Master Capability Request(“GMCapabilityRequest”) objects. The General Master CapabilityRequirement interacts with the “CapabilityClass”, and “Capability”objects and the General Master Unit interacts with the Equipment objectto determine a Master Design 115.

The specific equipment selection processing objects provide the system100 with the ability to map the General Design 111 to physical devicesand instrumentation; and to conduct a detailed analysis and validationof equipment fit. To accommodate error free transfer of execution recipeinformation to a variety of execution systems (such as Paper BatchBooks, Electronic Lab Notebooks, Distributed Control Systems,Manufacturing Execution Systems, etc.), facility specific PhaseDefinitions, Phase Maps, and Recipe Generators can be configured.

The Master Design 115 is the basis of Master Recipe 117, which isderived through shop floor execution system processing in Master Recipeobject 116. Referring to FIG. 9, shop floor execution system processinguses execution definitions, which are reusable software objects thatdefine execution objects and associated parameters that are specificallydesigned to be the building blocks for batch execution recipes. Phasedefinitions are reusable software objects that define the executionobjects and associated parameters that are specifically designed to bethe building blocks for batch execution recipes. Phase maps aresearchable records that map one or more generic phases to one or morephase definitions. The system may find the highest priority phase mapsand add the corresponding phase object instances to a Master Design. Itmay then invoke the dynamic code within each phase definition togenerate default parameter values which are derived from associatedgeneric phases. A user can optionally remove an applied phase map andthe associated object instances and apply a different phase map. Aplant-specific recipe generator may then create a recipe using theMaster Design structure which includes phase objects and theirparameters

FIG. 9 shows the sequence of actions of operation 148 previouslyintroduced in FIG. 2 and associated execution maps for each genericphase. Execution maps are searchable records that map one or moregeneric phases to one or more execution definitions. The systemidentifies the highest priority execution maps and adds thecorresponding execution object instances to a process design. Dynamiccode within each execution object is invoked to generate defaultparameter values which are derived from associated generic phases. Thepluggable execution system Master Recipe 116 object is then invoked tocreate the Master Recipe 117 using the process design structure whichincludes execution objects and their parameters.

A UML Class Diagram showing shop floor execution system processing inMaster Recipe object 116 in system 100 is illustrated in FIG. 10. InFIG. 10, the Library Data Scope 132 in this view shows the“ResourceClass”, “CapabilityClass”, “GenericPhaseDefinition” and“GenericPhasePortDefinition”, “EquipmentClass” and “OperationDefinition”objects. These objects in turn receive data from “PhaseCreationTemplate”object in Reference Data Scope 134. The Phase Creation Templateinteracts with the “PhaseDefinition” and through it, the“PhaseDefinitionParameterDefinition” object. The General Master GenericPhase object initiates the PhaseCreationTemplate object and the MasterRecipe Phase (“Mphase”) to create the Master Recipe 116 using the“PhaseDefinition”, “MPhaseDynamicParameter” and“PhaseDefinitionParameterDefinition” objects.

The shop floor execution system objects permit the system 100 to providea user with rapid mapping of the General Design to manufacturingexecution and control systems at a particular plant; and also provide afeedback and quality control system by providing mapping of theexecution history (discussed below) back to the Master Design and byreference through the design genealogy hierarchy back to the GeneralDesign, allowing continuous improvement of the process design.

Equipment instrumentation may be used to obtain process parametermeasurements. The instrumentation process parameter measurement data isreceived by manufacturing execution systems, SCADA systems, anddistributed control systems with batch execution objects to produceexecution history records. Desirably, the execution history recordsinclude the Master Design GUIDs that were previously included withinimported recipes. Process parameter measurement data 126 includes but isnot limited to task execution event history, execution alarm history,operator action history, material transaction history, and sample testresults. Raw history data may be aligned and extrapolated to compensatefor time domain fluctuations.

Process parameter measurement data 126 which is recorded in Process DataArchive 130 is correlated to one or more of the General Design 111, theGeneral Master Design 113, the Master Design 115, and the Recipe 117. Inmost instances correlation occurs at the Master Design 115 level. Thecorrelation determines variances and anomalies, including but notlimited to: unexpected equipment/resource utilization; out of sequencetask execution; skipped execution tasks; unexpected duplicate executiontasks; unexpected execution tasks; parameter value discrepancies;constraint violations; unexpected delays between execution tasks; andunexpected execution task durations.

A UML Class Diagram showing execution history correlation processing insystem 100 is illustrated in FIG. 11. In FIG. 11, the History Data Scope176 includes a “BatchHistory” object which containsBatchSegmentHistory”, UnitHistory”, “OperationHistory”, and“PhaseHistory” objects, as well as a “HistoryParameter” object. Ahistory of each measured parameter is recorded in these objects. TheLibrary Data Scope 170 includes “UnitDefinition” and Unit DefinitionParameter Definition (“UnitDefParamDef”); and “OperationDefinition” andOperation Definition Parameter Definition (“OperDefParamDef”) objects.The Reference Data Scope 172 includes “PhaseDefinition” and PhaseDefinition Parameter Definition (“PhaseDefParamDef”) objects, along with“ParameterCollectionDefinition” and a Definitions to ParameterCollection Definition Map (“DefToPCDMap”). The Design Data Scope 174contains the Master Recipe Design (“MDesign”), which in turn containsthe Master Recipe Unit (“MUnit”) and Master Recipe Unit DynamicParameter (“MUnitDynParam”), Master Recipe Operation (“MOperation”) andMaster Recipe Operation Dynamic Parameter (“MOperationDynParam”), MasterRecipe Phase (“MPhase”) and Master Recipe Phase Dynamic Parameter(“MPhaseDynParam”), and a Task to Parameter Collection Definition Map(“TaskToPCDMap”).

The execution history objects provide system 100 with the ability tovalidate the as-run batch process against the process design; to conducta comprehensive quality review without the need for data cleansing; andto conduct accurate performance assessments. A persistent correlatedexecution history that contains links to process design objects providesan anomaly/exception analysis tool. The software interface can displayall detected anomalies and correlation to the related process designstructure. The user can then add review comments to explain anomalyimpact on the batch; add missing execution history or correct existingexecution history; and/or re-process the history correlation algorithmon the batch with the updated execution history.

The system provides the user with the ability to compare processexecution on different batches. For example, each generic phase (oraction), use of equipment, and use of material may be independentlytracked, although not limited thereto. This allows the system todetermine deviations that result in different batch results (for betteror worse). This information may then be used to refine the processdesign by taking advantage of this historical data. For example, adeviation that results in an improvement may be added to the design. Adeviation that results in a worsening in yield, for example, mayindicate that an additional constraint should be added to the design toprevent the deviation in the future.

The execution history objects further provide the system 100 withversion correlation analysis. Process designs may change from time totime due to equipment changes and optimization opportunities or when thedesign is transferred from one facility to another. Each process designis determined and recorded with a different identifier. For example,different versions of the General Design 111, the General Master Design113, and the Master Design 115 are identified with a distinctidentifier, for example, version IDs such as v1.0, 1.1, 1.2, etc.Accordingly, designs may have ‘Version Shared IDs’ that point toprevious versions. A new version of a design can be created by copyingor deriving from a higher level design. The Version Shared IDs can beused facilitate comparative analysis.

Since the execution history objects are each correlated to differentprocess designs that share a common design genealogy, the executionhistory objects can be correlated automatically based on the identifier.The user can conduct comparative analyses of multiple process designswith a history correlation analysis using the execution history objects.Such correlations provide a persistent record of design evolutions and aknowledge transfer within one facility along a temporal axis, or betweenmultiple facilities along a geographic axis. A typical analysis of suchdata is mapping execution history objects to constraints. These datamaps for different versions are readily compared due to the VersionShared IDs.

Each of the system layers, including the General Design object 110, theGeneral Master Design object 112, and the Master Design object 114 canbe respectively operated to edit or manipulate the General Design 111,General Master Design 113, or Master Design 115, with changes on onelayer tested against the other layers to determine if any changesviolate any defined constraint. The different design construction modesof the systems include the following:

● Edit Mode: the user can add, modify, or edit entities. The userexperience may be driven by parameter definitions and specific designlevel editing rules.

● Simulation Mode: the user initiates a simulation process that isexecuted by the system where mass balance, energy balance, andtime-cycle data is refreshed for all valid entities. Invalid entitiesmay be marked as such and validation results presented.

● Review Mode: the user explores and analyzes the current design resultsby using multiple interactive design views to decide on the nextconstruction steps.

The edit mode may enforce the three level hierarchy (General Design,General Master, and Master) where only specific editing features arepossible. The following are some examples: 1) General Design 111 Updates

-   -   a. Modify or add a new Regulatory Constraint    -   b. Modify or add a new General Operation 2) General Master        Design 113 Updates    -   a. Modify or add a new Quality Constraint    -   b. Add General Master Generic Equipment Units, move existing        General Master Operations, and add new General Master Operations    -   c. Modify the equipment candidate list    -   d. Rescale the design 3) Master Design 115 Updates    -   a. Modify Phase Map selection and modify Phase parameters    -   b. Modify an equipment selection    -   c. Rescale the design within the constraints of the design and        the equipment set

When the user decides to make a change at a higher level in the designhierarchy, they may be required to create a new version of the design atthat level and propagate the changes down to the next lower level (bycreating newer versions of the lower design levels).

For example, a user may copy the design refinements implemented in aprevious version of a General Master Design 113 and combine them withthe design refinements of a newer General Design 111 version. Thefollowing are the high level steps of an exemplary algorithm: 1) If NOT(GMDesign.GDesign.VersionSharedID =TargetGDesign.VersionSharedID)

-   -   a. GMDesign.Properties=TargetGDesign. Properties    -   b. GMDesign.Option=GetNextOption(GMDesign.Option) p1 c. Delete        GMDesign.GDesignOperationMaps 2) Else For Each        GMDesign.Operation    -   a. Find Mapped TargetGDesign Operation List    -   b. Delete Maps to TargetGDesign Operations that do NOT exist    -   c. If GDesign.Operation.VersionSharedID        =TargetGDesign.Operation.VersionSharedID        -   i. GDesign.Operation.Parameters            =TargetGDesign.Operation.Parameters 3) Delete            GMDesign.Reactions 4) GM Design.            Reactions=DeriveReactions(TargetGDesign) 5) GM            Design.Constraints=DeriveConstraints(TargetGDesign) 6)            GMDesign.VersionSharedID=NewGUID 7)            GMDesign.GDesignUID=TargetGDesign.UID 8)            LatestGMDesignVersion=GetLatestGMDesignVersion(Facility,            TargetGDesign) 9)            GMDesign.Version=GetNextVersion(LatestGMDesignVersion)

The simulation mode may include the following high level algorithm: 1)Check Task graph for Cycle Errors 2) Check Task graph for DeadlocksErrors 3) Check Task graph for Branching Errors 4) Check Task graph forGeneric Phase Mapping Errors 5) Validate Task graph

-   -   a. Get Invalid Task List    -   b. Setup Resources based on Resource Requirements    -   c. Generate Task events for invalid Tasks in graph order 6) Run        Simulation    -   a. For Each Task Event        -   i. Call Task Refresh Parameters Function (Dynamic Code)        -   ii. Call Task Validate Function (Dynamic Code)        -   iii. If Validate Error occurred            -   1. Invalidate the Task and all downstream Tasks        -   iv. Else            -   1. Clear any outstanding Task resource acquires            -   2. Get Task consolidated resource requirements via                resource requests that are associated with capability                requests            -   3. Acquire Task resources            -   4. Call Task Simulate Function (Dynamic Code)            -   5. Release Task resources            -   6. Perform Material Specification Transformations if any                exist 7) If all Tasks simulated, collect Resource Usage                Data 8) For Each Unit    -   a. If Equipment selected, retrieve parameters from selected        components    -   b. Calculate unit volume utilization 9) Collect Material        Transfer Records 10)Calculate Batch Size 11)Calculate Batch        Yield 12)Calculate Time Cycle Data 13) For Each Task (in graph        order), call Task Refresh Parameters Function (Dynamic Code)        14)For Each Constraint, call Constraint Validate Parameters        Function (Dynamic Code) 15) Return Validation Results

Referring now to FIG. 12, shown is an illustration of a layout for agraphical UI (User Interface) 190 of the Design System 102 of system100. The UI may include a number of several visual components.Generally, the UI 190 may comprise a design view 200, a process flowview 202, time cycle view 204, and an instructions view 206, althoughnot limited thereto. A design view 200 may provide a visual indicator ofall of the operations laid out under the equipment units. The user mayuse the UI 190 to create operation entities and connections betweenoperation port entities manually, and the design software may creategeneric phase entities and connect generic phase port entities aspreviously described.

Referring now to FIGS. 13A-D, shown are examples of the graphical userinterface according to FIG. 12. The right side of FIG. 13A shows“Design” view 200 which includes units and operations, “Process Flow”view 202 which includes equipment and connections, “Time Cycle” view 204(a Gantt chart of the manufacturing time cycle), and “Limits View” 210(constraints). The left side of FIG. 13A shows subviews 208 including PVTrend, Instructions 206 (Master Recipe 117), and a unit state subview.FIG. 13B is a detail view of the PV Trend (a process variable chart)subview. FIG. 13C is a detail view of “Instructions” view 206 (a MasterRecipe 117 instruction set). FIG. 13D is an example of a unit statesubview (a reagent mass balance chart). Each window shows datapertaining to an exemplary ‘Distill’ operation. A system according tothe present teachings may provide interactive GUI elements. Engineerscan adjust design inputs and all elements are updated when the design isre-simulated. This way, changing some process information andre-simulating the design provides the user instant feedback on theimpact of the change. The system automatically updates all associatedinternal and UI objects (e.g., Instruction View, Process Flow Diagram,Time Cycle View, Auxiliary Information Panels, etc.) to reveal thedirect and indirect impact of design changes.

FIGS. 14-17 show embodiments of the graphical user interface 190 fordesigning and planning product manufacturing according to design system102. FIG. 14 shows one embodiment of the user interface 190 for theGeneral Design 110 layer of system 100. FIG. 15 shows one embodiment ofthe user interface 190 for the General Master Design 112 layer of system100. As previously disclosed, the General Master Design 112 layer isderived from the General Design 110 layer and inherits all constraintsand regulatory parameters. The General Master Design allows genericequipment-level detail. Process operations are further broken down tomore discrete “generic phases” (or “actions”). FIG. 16 shows oneembodiment of the user interface 190 for Master Design 114 layer ofsystem 100. The Master Design 114 layer is derived from the GeneralMaster Design 112 layer inherits all constraints and regulatoryparameters of both the General Master Design 112 layer and the andGeneral Design 110 layer. FIG. 17 shows one embodiment of the userinterface for product planning. A product planner may compile variousreports from multiple designs to enable a cross-product view of usefulmetrics. The user can see the impact on the metrics as differingquantities of product are manufactured. Metrics include those related tocost, equipment utilization, productivity, and environmental, althoughnot limited thereto. In this way, different production scenarios can beeasily compared.

The design process may include the construction of a process flowdiagram that allows the user to easily explore the equipment,inter-equipment connections, and material transfers. The process flowview 202 may provide for process flow processing. Tracking key materialthrough the simulation may identify key equipment units. The processflow algorithm may have 3 phases:

● Phase 1: Key equipment is positioned in the center following keymaterial processing flows from left to right.

● Phase 2: Feed equipment is positioned above the line and receiverequipment below the line.

● Phase 3: Connection routing is performed between equipment outlets andinlets to minimize line overlaps.

The above phases may include the following steps:

-   -   1) Phase 1        -   a. Calculate a process flow index for all equipment based on            key/product material flow        -   b. Separate equipment into connected groups        -   c. For each equipment group            -   i. Use process flow index to calculate initial column                positions of key equipment from left to right            -   ii. Find cyclical equipment connections and break them            -   iii. For each key equipment                -   1. Find input equipment and output equipment and                    create key equipment group                -   2. Recursively calculate column and row position for                    all input equipment that positions them above and to                    the left of the key equipment                -   3. Recursively calculate column and row position for                    all output equipment that positions them below and                    to the right of the key equipment            -   iv. Recalculate column and row positions for all                equipment        -   d. Recalculate column and row positions for all equipment            groups        -   e. Optimize empty space by compressing horizontally    -   2) Phase 2        -   a. For each equipment from left to right            -   i. Sort ports based on target/source type:                -   1. key equipment;                -   2. secondary equipment;                -   3. equipment row;                -   4. equipment column;                -   5. none            -   ii. Route connection lines between output ports and                inlet ports using up to 3 stages:                -   1. Horizontal right;                -   2. Vertical down; and                -   3. Horizontal right;    -   3) Phase 3        -   a. Calculate absolute position of all objects based on            object size and required spacing        -   b. Draw connections

A time cycle view 204 (seen in FIGS. 13A and 14 (middle panel)) for theprocess may be displayed in the form of a Gantt chart. This may becalculated to aid in the visualization of task timing information, thecritical path, and task dependencies. The key data items are start time,end time, slack time, duration and connections for each design task.

An instruction view 206 (seen in FIGS. 13C and 16 (lower panel)) mayprovide recipe instructions and other subviews (tabbed auxiliaryinformation panels or screens) 208, which may include tabular reports ofvarious pieces of information. An instructions subview may display adescription of each generic phase. Selecting a design task may displaythe instructions that are associated with it on this subview. If aninstruction on the subview is selected, the design tasks that the textcorrelates to may be highlighted (or given some other designation).

A unit state subview (seen in FIG. 13D) may show an overall materialbalance and also a material balance on the individual materials. Alsoshown may be the expected temperature, volume and specific gravity. Astate variables section may display parameter values associated with theselected design task, and a time cycle section may display timeinformation, such as start time, end time and duration for the selecteddesign task. A mixture section on a unit state subview may display thematerial balance. By clicking on a generic phase, the material balanceat the end of the generic phase may be displayed.

A reactions subview may display all the reactions that take place withinthe design. When this subview is selected, the generic phase(s) wherethe reaction(s) are scheduled to take place may be highlighted (or givensome other designation).

A limits subview (seen in FIG. 13A, lower panel) may display theconstraints that are imposed upon the design. At the general designlevel, all constraints may be regulatory. In a General Master Design,however, there can be quality and process constraints which createtighter ranges. Clicking on a design task may show the constraintsassociated with that task and clicking on the background may show allconstraints in the design.

A validation subview may be responsible for displaying simulationmessages to the user regarding the current design. Each message maycontain the message result as well as its type and a description of theerror. The message result can be of several types such as, for example:

● Info—States information regarding the design to the user.

● Warning—Informative message that does not need to be resolved tocomplete the design.

● Error—Problem with the design that must be resolved prior tocompleting the design.

The message type can be of several different types such as, for example:

● Completeness—Indicates a problem in the design which must be resolvedprior to marking the design complete.

● Limit—Indicates a problem related to one of the constraints defined inthe design.

● Not Provided—Indicates that required information is not provided tothe design.

● Operation—Indicates a problem related to one of the operations in thedesign.

● Generic Phase—Indicates a problem related to one of the generic phasesin the design. (General Master Design)

● Generic Phase Mapping—Indicates an error or warning while mappinggeneric phases. (Master Design)

● Phase—Indicates a problem related to one of the phases in the design.(Master Design)

● Referential Integrity—Indicates a problem with the references from achild design to its parent design. An example of this would be a GeneralMaster operation which is not mapped to a parent general operation.

● Structural Integrity—Indicates a problem with the structure of thedesign. This may be related to the presence of a disconnected unit, aloop or a deadlock within the design.

A material summary subview may describe the charges and dischargesassociated with the design (e.g., General Master Design). The subviewmay display each material used in the design, as well as how much wascharged/discharged. The user may expand a material usage record toreveal the individual charges by generic phase along with the percentageof the total design charge. By clicking on the material, the designtasks associated with that charge/discharge may be highlighted in otherdesign views (or given some other designation). The material summarysubview also may have sections regarding intra-unit transfers andemissions. The intra-unit transfers section may display informationregarding the transfer of materials from one unit to another. Theemissions section may display emissions output for each generic phase inthe design.

Designs may change from time to time due to equipment changes andoptimization opportunities. Execution history that is correlated todifferent process designs that share a common design genealogy can becorrelated by using methods such as, for example:

● Using global operations Version IDs (“VIDs”). VIDs may be maintainedwhen a process design is copied or versioned.

● Using global operation group IDs (collection of sequential operationsthat represent a general process stage)

The user can optionally select operations from multiple designs manuallyto initiate a history correlation analysis.

Designs may be transferred between manufacturing plants using a systemaccording to the present teachings. Design objects may be removed fromGeneral Master Designs that will be copied to other facilities such as,for example:

● Phase maps and phase objects

● Resource selections

● Equipment selections

● Facility specific resource injections

● Facility specific equipment capability specializations

Target facility equipment specialization and resource injection rulesmay be processed before the design is saved. If the target facility doesnot have equipment that is compatible with the General Master Design,the user can perform the optional changes to transform the design suchas, for example:

● Modify unit equipment classes (this action may generate validationerrors that must be resolved by modifying operations or using differentoperations)

● Modify operation parameters

● Move operations to different units or new units

If the target facility is in a different enterprise, then the user canoptionally create the foreign source facility and save the designwithout modification.

To accommodate error free transfer of execution recipe information to avariety of execution systems (such as Paper Batch Books, Electronic LabNotebooks, Distributed Control Systems, Manufacturing Execution Systems,etc.), facility specific phase definitions, phase maps, and recipegenerators may be configured.

Design transfer between facilities within the same enterprise isrelevant to General Master Designs and may be accomplished using thefollowing algorithm: 1) If the design contains selected equipment removeall equipment 2) Remove all capability requirements and resourcerequirements 3) Execute capability specialization rules from the targetfacility 4) Execute capability request consolidation rules to createcapability requirements 5) Execute resource injection rules from thetarget facility 6) Execute resource request consolidation rules tocreate resource requirements 7) Save the a new version of the GeneralMaster Design in the target facility

Design transfer between enterprises may be accomplished by exporting adesign package that contains the design, all associated reference data,and all associated library data. The receiving enterprise imports thepackage. The package import algorithm may perform the following actions,although not limited thereto: 1) If the target site facility does notexist, create a site database 2) If the target plant facility does notexist, create it inside the target site database 3) If the targetequipment does not exist in the target facilities, create it in thetarget facilities 4) If the target materials, reactions, and productsteps do not exist in the global facility, create them 5) Create thetarget design

Using the system, users may easily scale design models. Scaling refersto the changing of the quantity of material that is used or produced bya design. Typically, the quantity of material consumed by a GeneralMaster Design will be different from the quantity consumed by a GeneralDesign because plant engineers will be exploring optimum batch size/timecycle combinations. Therefore, the ability to scale designs upward ordownward is desirable. If a user wants to scale a design, they may clicka scale button.

The system may allow the scaling of designs in a number of ways such as,for example:

● Scale to a specified scale factor—This may scale the design accordingto the value input by the user (e.g., a factor of 10 would multiplyscalable mass values in the design by 10).

● Scaling to target batch size—When scaling to a target batch size(mass), the scaling ratio may be determined by identifying the ratiobetween the original batch size (mass) and the target batch size (mass).All “Charge” operations within the design may then be scaled using thisratio—with the exception of non-scalable materials.

● Scaling to maximum batch size—The design may be scaled according tothe maximum batch size.

● Scaling to target unit volume—This may calculate the scaling ratio bydividing the target unit volume by the maximum mixture volume of theselected unit. This scaling ratio may then be applied across the design.Volume scaling may be assumed to be linear; the effects of pressure andtemperature may be ignored for the purpose of volume scaling.

When scaling a design, non-scalable mass values may be left unchanged.Examples are fixed wash or rinse charge quantities. The system canhandle the full range of scalability, from lab scale to full-scaleproduction volumes. As such, calculations may not entail rounding,except for the purpose of display. Scaling has an impact on unit statesand time cycles within simulation streams and therefore, the system mayinvalidate the entire design after user initiated scaling. The user mayperform a design re-simulation to revalidate the design after scaling.

While the present teachings have been described above in terms ofspecific embodiments, it is to be understood that they are not limitedto these disclosed embodiments. Many modifications and other embodimentswill come to mind to those skilled in the art to which this pertains,and which are intended to be and are covered by this disclosure. It isintended that the scope of the present teachings should be determined byproper interpretation and construction of this disclosure and its legalequivalents, as understood by those of skill in the art relying uponthis specification and the attached drawings.

What is claimed is:
 1. A method of chemical, biological, orpharmaceutical process design and management executed on a computerhaving a storage on which a process library is saved, the processlibrary including material data, process data, and equipment data, themethod utilizing computer readable instructions performing the steps of:receiving a General Design defining operations sequences, and processingoperation parameters including materials balances, cycle time andconstraints for manufacturing a chemical, biological, or pharmaceuticalproduct based on user input data and retrieved process library data;executing a General Master Design defining operations equipmentsequences, and processing operation parameters including equipment,generic equipment capability requirements, materials balances, cycletime and constraints for manufacturing a chemical, biological, orpharmaceutical product; and executing a Master Design definingoperations equipment sequences, and processing operation parametersincluding specific equipment, specific equipment capabilityrequirements, actual capacity analysis, materials flows and balances,cycle time and constraints for manufacturing a chemical, biological, orpharmaceutical product.
 2. The method of claim 1, wherein the step ofexecuting a General Master Design further comprises: defining genericphases of the equipment process.
 3. The method of claim 2, wherein thestep of executing a Master Design further comprises: mapping genericphases to specific phases for specific execution systems in a specificmanufacturing facility.
 4. The method of claim 1, further comprising thestep of creating a Master Recipe.
 5. The method of claim 4, furthercomprising the step of: controlling a chemical, biological orpharmaceutical manufacturing process in accordance with the MasterRecipe through one or more of a manufacturing plant distributed controlsystem, laboratory information management system, manufacturingexecution system (“MES”).
 6. The method of claim 5, further comprisingthe steps of: measuring process parameters; storing process parametermeasurement data in a process data archive; and correlating processparameter measurement data to the Master Design to determine variancesor anomalies.
 7. The method of claim 1, further comprising the step oftransferring a process design from a first manufacturing facility to asecond manufacturing facility.
 8. The method of claim 7, wherein thestep of transferring the process design comprises the steps of: storinga generic equipment process derived by the General Master Design in thestorage; retrieving the stored generic equipment process from thestorage; executing the Master Design to derive a new plant-specificequipment process correlated to the second manufacturing facility. 9.The method of claim 1, wherein the General Design, the General MasterDesign and the Master Design are stored on the storage.
 10. The methodof claim 1, wherein the computer is selected from the group consistingof: a digital signal processor, a field-programmable gate array, anapplication-specific integrated circuit, a micro-processor, amicro-controller, or any other form of programmable hardware.
 11. Themethod of claim 1, further comprising the step of generating amanufacturing process design based on user input data and retrievedprocess library data using a graphical user interface for the computer.12. The method of claim 11, wherein the graphical user interface allowsmultiple views of the manufacturing process design.
 13. The method ofclaim 12, wherein the views include one or more of: a design view, aprocess flow view, a time cycle view, and an instructions view.
 14. Themethod of claim 13, wherein the views are defined by one or more of thefollowing: the design view identifies each equipment unit and listschemical, biological or pharmaceutical process operations with eachequipment unit; the process flow view displays inter-equipmentconnections and material transfers for the process; the time cycle viewdisplays start time, end time, slack time and duration for eachoperation of the process in order; and the instructions view displaysmanufacturing instructions which list all required inputs and steps ofthe chemical, biological or pharmaceutical process.
 15. The method ofclaim 13, wherein the design view, process flow view, and time cycleview dynamically interact with each other such that a change in one viewwill result in a corresponding change in the others.
 16. The method ofclaim 1, further comprising the step of validating the process design byexecuting a process simulation.
 17. The method of claim 1, furthercomprising the step of: assigning globally unique identifiers to eachprocess ingredient and process step; wherein data relating to theingredients and the process steps is stored enabling a correlatedexecution history.
 18. A method of chemical, biological, orpharmaceutical process design and management executed on a computerhaving a storage on which a process library is saved, the processlibrary including material data, process data, and equipment data, themethod utilizing computer readable instructions performing the steps of:executing a General Master Design defining operations equipmentsequences, and processing operation parameters including equipment,generic equipment capability requirements, materials balances, cycletime and constraints for manufacturing a chemical, biological, orpharmaceutical product based on user input data and retrieved processlibrary data; and executing a Master Design defining operationsequipment sequences, and processing operation parameters includingspecific equipment, specific equipment capability requirements, actualcapacity analysis, materials flows and balances, cycle time andconstraints for manufacturing a chemical, biological, or pharmaceuticalproduct.
 19. The method of claim 18, wherein the step of executing aGeneral Master Design further comprises: defining generic phases of theequipment process.
 20. The method of claim 19, wherein the step ofexecuting a Master Design further comprises: mapping generic phases tospecific phases for specific execution systems in a specificmanufacturing facility.
 21. The method of claim 18, further comprisingthe step of creating a Master Recipe.
 22. The method of claim 21,further comprising the step of: controlling a chemical, biological orpharmaceutical manufacturing process in accordance with the MasterRecipe through one or more of a manufacturing plant distributed controlsystem, laboratory information management system, manufacturingexecution system (“MES”).
 23. The method of claim 22, further comprisingthe steps of: measuring process parameters; storing process parametermeasurement data in a process data archive; and correlating processparameter measurement data to the Master Design to determine variancesor anomalies.
 24. The method of claim 18, further comprising the step ofgenerating a manufacturing process design based on user input data andretrieved process library data using a graphical user interface for thecomputer.
 25. The method of claim 24, wherein the graphical userinterface allows multiple views including one or more of: a design view,a process flow view, a time cycle view, and an instructions view. 26.The method of claim 25, wherein the views are defined by one or more ofthe following: the design view identifies each equipment unit and listschemical, biological or pharmaceutical process operations with eachequipment unit; the process flow view displays inter-equipmentconnections and material transfers for the process; the time cycle viewdisplays start time, end time, slack time and duration for eachoperation of the process in order; and the instructions view displaysmanufacturing instructions which list all required inputs and steps ofthe chemical, biological or pharmaceutical process.
 27. A method ofchemical, biological, or pharmaceutical process design and managementexecuted on a computer having a storage on which a process library issaved, the process library including material data, process data, andequipment data, the method utilizing computer readable instructionsperforming the steps of: receiving a General Master Design definingoperations equipment sequences, and processing operation parametersincluding equipment, generic equipment capability requirements,materials balances, cycle time and constraints for manufacturing achemical, biological, or pharmaceutical product based on user input dataand retrieved process library data; and executing a Master Designdefining operations equipment sequences, and processing operationparameters including specific equipment, specific equipment capabilityrequirements, actual capacity analysis, materials flows and balances,cycle time and constraints for manufacturing a chemical, biological, orpharmaceutical product.
 28. The method of claim 27, wherein the step ofexecuting a Master Design further comprises: mapping generic phases tospecific phases for specific execution systems in a specificmanufacturing facility.
 29. The method of claim 27, further comprisingthe step of creating a Master Recipe.
 30. The method of claim 29,further comprising the step of: controlling a chemical, biological orpharmaceutical manufacturing process in accordance with the MasterRecipe through one or more of a manufacturing plant distributed controlsystem, laboratory information management system, manufacturingexecution system (“MES”).
 31. The method of claim 30, further comprisingthe steps of: measuring process parameters; storing process parametermeasurement data in a process data archive; and correlating processparameter measurement data to the Master Design to determine variancesor anomalies.